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Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
Nusinersen is an oligonucleotide that modifies splicing of the SMN2 gene to increase production of normal, full-length SMN protein. It is administered intrathecally with four loading doses over 8 weeks followed by maintenance dosing every 4 months. In a multicenter, double-blinded trial, improvement in motor milestones as measured by the Hammersmith Infant Neurological Examination was observed in 37 of 73 (51%) infants receiving nusinersen vs. 0 of 37 (0%) infants receiving sham therapy. They were also less likely to die or receive permanent assisted ventilation (39 vs. 68%) [31].
Spinal Cord Disease
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Nusinersen is an antisense oligonucleotide treatment used in the treatment of SMA. The drug acts on SMN2 to increase SMN2 expression and reduce the severity of the SMA disease phenotype. It is given as an intrathecal injection, which complicates its administration logistically. In clinical studies, nusinersen led to an improvement in motor milestones in infants receiving the drug in trials.
Practical Considerations for Building Priors for Confirmatory Studies
Published in Mani Lakshminarayanan, Fanni Natanegara, Bayesian Applications in Pharmaceutical Development, 2019
Guochen Song, John Zhong, Stacy Lindborg, Baoguang Han
The CS3A study (Finkel et al., 2016) was a Phase 2, multicenter, open-label, multiple-dose, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of nusinersen administered intrathecally to patients aged ≤7 months who had clinical signs and symptoms of SMA at ≤6 months of age at Screening. The original design of the study was to follow patients every 2–3 weeks for 36 weeks, and the protocol was amended to have the telephone follow-up up to 2.5 years.
Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database
Published in International Journal of Neuroscience, 2023
Takafumi Wataya, Sakura Takasaki, Misuzu Hoshino, Haruki Makioka, Genshu Nakamura, Naoto Matsuda
Importantly, the most common types of AEs in the clinical studies and in both the PMS and the Biogen safety database were generally similar. The integrated safety analyses from the clinical trials with nusinersen found that most AEs were not related or unlikely to be related to the treatment [25, 26], and the most common AEs occurring during nusinersen treatment were respiratory infections and lumbar puncture reactions, such as vomiting and (in those with later-onset SMA) headache [25, 26]. Our study also found that respiratory infection or upper respiratory tract inflammation were common. Nusinersen is delivered via lumbar puncture and intrathecal injection, and the frequency of AEs related to lumbar puncture in SMA patients receiving nusinersen was similar to that previously reported in patients undergoing lumbar puncture for other indications [28]. Only one patient in our PMS analysis developed vomiting, which sometimes occurs with lumbar puncture [29], but other lumbar puncture-related events were reported, including cerebrospinal fluid (CSF) leakage in three patients. In the safety database, four events of CSF leakage and five events of vomiting were reported. Cases of meningitis associated with the lumbar puncture procedure, hydrocephalus, and hypersensitivity have been reported during the use of nusinersen in the real-world clinical setting [30], including one case of hydrocephalus in an infant recorded in the current analysis of safety data. The occurrence of hydrocephalus in untreated children with SMA is not well understood.
Outcomes in patients with spinal muscular atrophy given nusinersen, onasemnogene abeparvovec or no treatment: an analysis based on restricted mean survival time
Published in Expert Opinion on Orphan Drugs, 2020
Nusinersen is an antisense oligonucleotide specifically designed to alter splicing of SMN2 pre-mRNA, increasing the amount of functional survival motor neuron. It is administered by intrathecal injection and the treatment requires multiple loading doses followed by a maintenance dose. OAX is an adeno-associated virus vector-based gene therapy designed to replace the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN1 gene. The treatment consists of a one-shot intravenous administration.
New treatments in spinal muscular atrophy: an overview of currently available data
Published in Expert Opinion on Pharmacotherapy, 2020
Sithara Ramdas, Laurent Servais
Nusinersen was the first drug clinically approved for the treatment of SMA. It was approved by the US Food and Drug Administration (FDA) in late December 2016 and by the European Medicines Agency (EMA) in June 2017. Nusinersen expanded access programs (EAPs) were initiated in several countries while drug approval was being sought. Data published from several EAPs confirm therapeutic benefit with motor function improvements [36–40]. Nusinersen is overall a safe drug but there are some reports of hydrocephalus [36–41].